MDFIC2 is a PIEZO channel modulator that can alleviate mechanical allodynia associated with neuropathic pain
Bibliographic record
Abstract
PIEZO channels are mechanical force sensors involved in various biological processes, including somatosensation. To date, only a few PIEZO-binding partners have been identified, including MyoD-family inhibitor proteins (MDFI and MDFIC). Here, we show that MDFIC2, a third member of the MDFI protein family with an as-yet-unknown function, is expressed in a subset of nociceptive sensory neurons. MDFIC2 modulates both PIEZO1 and PIEZO2 gating properties by slowing their kinetics and shifting mechanical sensitivity to higher forces. Interestingly, Mdfic2 is downregulated in mouse neuropathic pain models in which mechanical allodynia is a hallmark symptom. We found that intrathecal administration of adeno-associated virus vector encoding MDFIC2 cDNA reduces mechanical sensitivity and attenuates mechanical allodynia in the spared nerve injury neuropathic pain model. These findings demonstrate a mechanism for regulating mechanosensation and highlight a potential therapeutic route for treating mechanical allodynia.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".